Clinical features and treatment of methylmalonic acidemia complicated with Dandy-Walker continuum: a report of 4 cases and review of literature

Purpose The clinical characteristics and treatment of the rare methylmalonic academia (MMA) with Dandy-Walker continuum (DWC) are still unclear. The purpose of this paper is to provide novel insights into the rare pediatric disease. Methods The database of MMA cases from pediatric intensive care unit of our hospital from 2006 to 2021 was chosen, from which cases combined with DWC were selected. The characteristics of onset age, clinical manifestations, gene types, treatment and prognosis of these cases were analyzed. The diagnosis of MMA was confirmed by blood and urine tandem mass spectrometry while the diagnosis of DWC was confirmed by cranial magnetic resonance imaging (MRI). Follow-ups were performed by means of telephone inquiry or outpatient visit. Results A total of 198 children with MMA were screened, 4 of whom were complicated with DWC including 3 males and 1 female. The average age of onset was 38 days (range 4–60 days). Vomiting (3/4) was the most obvious symptom. The head circumference was small in 2 cases while normal in the rest. The blood homocysteine was 130.8-187.3 umol/L, and the urine MMA was 24.5-236.1 mmol/mol·creatinine. Blood C3 and C3/C2 levels were significantly increased in 4 children. MRI showed that the cerebellar vermis was dysplastic, and cystic dilatation of the fourth ventricle caused upward displacement of the tentorium and sinuses. All the 4 children were treated with drugs and special milk powder for the primary disease. Case 3 suffered from acute intracranial pressure (ICP) increase during hospitalization, resulting in respiratory and circulatory failure, and was treated with dehydration, lowering ICP and ventilator-assisted ventilation. However, these measures had minimum effect, and the patient died of multiple organ dysfunction syndrome 27 days after admission. In case 1, 2, and 4, ventriculoperitoneal shunt (VPS) was performed for the increased ICP. Case 1 died of respiratory failure 10 months after the operation, while case 2 died of severe pneumonia 96 months after the operation. Unlike the others, case 4 remained stable condition at the last follow-up of 32 months. Conclusions Concomitant DWC may be a clinical manifestation type of MMA, with early onset and severe conditions. The onset of increased ICP can often be seen. Head circumference can be in normal limits, and they can be manifested as hydrocephalus. VPS should be actively performed to treat hydrocephalus, relieve elevated ICP and improve the prognosis.